migraine Migraine comes from the Greek ‘hemicrania’, or half-sided headache, and is in essence a form of ‘primary headache’, which is to say that the headache is itself the disorder and is not secondary to some other process, such as infection or injury. Migraine has been recognized throughout recorded history and there are reasonably clear descriptions that date back to Sumarian times. Migraine is as real as high blood pressure or a broken bone. It is an important, biologically-based disorder that should never be thought of as psychosomatic. Migraine is characterized by episodes of often severe, usually one-sided, frequently throbbing or pounding pain, associated with other features, such as nausea or vomiting, sensitivity to body movement, sensitivity to light (photophobia), or sensitivity to sound (phonophobia).

Migraine is probably best viewed as an inherited tendency to have headache, or perhaps headacheyness, rather than just the limited view of episodes of severe headache. Certainly many migraine patients suffer very severe, disabling headache that does not shorten life but can make it virtually a living hell. However, a broader view is necessary to explain everything that the physician encounters, and other aspects of the problem may dominate in the individual.

The frequency of migraine varies greatly between individuals — occurring almost every day, once or twice a year over many years, or just a few times in a whole lifetime. The biology of migraine does not always obey the rather strict rules that have been evolved to describe it: although these are very useful for research, one should not be a slave to rules for a problem with such a complex biology.

The cause and incidence of migraine

Migraine is probably for the most part inherited. It is thought to be autosomal dominant (see genetics, human), which means that about half the children of an affected parent will carry the genes irrespective of sex. Its expression in any one patient varies and so while most migraine sufferers will have an affected relative this is not always the case. Migraine can start at almost any time in life but the peak incidence is in the 20s and 30s. About 4–6% of children are affected, slightly more boys than girls, and about 10% of most adult Caucasian populations that have been studied. Probably fewer people are affected in African populations, and fewer still in oriental Asian populations. At puberty, with the onset of menstrual periods, the prevalence (number of people with the problem) of migraine increases in females and remains greater than in males right up to the 80s. The peak prevalence is about the age of 40; in this age-group about 1 in 5, or 20%, of adult Caucasian women have migraine. This is an enormous public health issue that has barely been addressed, yet has been with humans for several millennia.

Migraine aura — the flashing lights and zigzags

Migraine aura is a very special part of the problem that affects only about 20% of sufferers. It consists of zigzag flashing lights, loss of vision, bright sparkles, pins and needles over the face or arms, or even weakness, speech problems, or balance problems. Aura usually comes at the beginning of an attack and lasts about 30 min; less commonly it can occur during or even after the headache; it very rarely lasts more than an hour. It has two very important features: firstly, it moves slowly across the field of vision, or up or down the limb, almost never moving suddenly; and secondly, it is completely reversible — it always gets better. Changes to such symptoms should result in prompt medical review. Recently, the nature of a very special, rare form of aura, called hemiplegic aura, involving complete loss of use of the limbs on one side, has been elucidated. It is often due to a mutation, a change in the gene for a particular protein that allows electrically charged chemicals into body cells and controls the release of messenger molecules in the brain. These mutations on chromosomes 1 and 19 are pointing to ways in which we might understand how ordinary migraine starts: this is an active area of research.

The pain of migraine

This does not have a single explanation, which is perhaps why it has been difficult to characterize precisely. The pain in migraine involves abnormal signals in nerve fibres from the large blood vessels in the head — both from those within the skull (brain blood vessels) and also some from outside the skull, as well as from the protective covering of the brain, the meninges, particularly the tough fibrous part, the dura mater. The brain does not feel pain itself but because of an episodic defect in the nerve systems that control pain and other signals coming into the brain, normal or somewhat abnormal signals are amplified. So a normal or slightly dilated blood vessel gives a pounding or throbbing pain, often in time with the pulse. The pain is felt on the forehead, behind the eyes, over the top, around the sides, or over the back of the head, because the nerves that take pain signals from all over the inside of the skull go to the same place in the brain stem, to the trigeminal nucleus. Just as it can be impossible to locate the source of pain arising from organs in the body cavities — the abdomen or the chest — so migraine pain can be all over the head, or just on one side, or just in one place, wherever the source of the signals. Pain location in migraine, particularly over the back of the head, does not therefore necessarily implicate that area as diseased. This applies, for example, to the neck, which is often blamed for migraine but is seldom the true cause. The poor location of pain from within body cavities, referencing it elsewhere, is called referral of pain, and is a well-established, important concept that also applies to migraine. Referral of pain takes place because pain fibres from a deep structure, (such as, in this case, a brain blood vessel), and a superficial structure (such as the skin), both project to the same nerve cell in the trigeminal nucleus. The body cannot thus distinguish where the signal comes from, and wrongly attributes, or ‘refers’, the pain to the skin or other superficial structure.

The other symptoms of migraine can be thought of broadly as sensitivities to various things: movement, noise, light, smells, even something in the stomach to cause nausea (although we currently think that nausea has an important component from connections of the pain nerves with nausea cells in the brain). The areas in the human brain that have been shown to be active in migraine have two very interesting roles in normal physiology. One area in the brain stem controls, ‘gates’, or modulates incoming sensory information. It allows us to concentrate on something and to ignore irrelevant noise or even tactile (feeling) information. It is likely that this area, called the nucleus locus coeruleus, dysfunctions in migraine so that normal light or sound are perceived by the brain as too bright or loud, or normal smells as unpleasant. Many migraine sufferers report that their brain seems clouded, they cannot concentrate, and their thought processes are just not right. It seems likely that it is abnormalities in the locus coeruleus and associated areas that form the basis of the biology of these very real symptoms. One of the areas shown by imaging techniques to be active in migraine is also active during sleep induction, so it is no surprise that migraine sufferers for thousands of years have appreciated the benefit of sleep.

Much has changed in our understanding of migraine in the last decade, such that sufferers can now be given a reasonable explanation of most of their symptoms and thus be optimistic that soon their disease will be even better understood.

Meanwhile, the main thing that sufferers can do is to understand their limits. Many triggers for migraine can be identified, such as stress. (However, stress can trigger just about any type of headache, and there can therefore be no distinct thing called stress headache.) Environmental situations, some chemicals and foods, and a host of other situations are patient-specific triggers. These triggers have one general theme. The migraine sufferer is less tolerant of altering circumstances — such as skipping meals or eating late (and this is particularly true of children). They may not tolerate stress but, in an apparent paradox, may also get headache when they relax, or when they over-sleep or under-sleep, or when they exercise too much or not enough. In short, the migraine sufferer must be a little more careful with their life and think out what situations they can avoid; this may apply particularly to women during the menstrual cycle.

The remedy then is to exercise, eat, and sleep regularly and perhaps, oddly enough, always have a little stress! If one has headaches on Saturday mornings, is it just because of ‘sleeping in’, or because of the sudden relaxation at the end of a hard week, or even a change in caffeine consumption? Often a simple solution is to get up at a similar time to the weekdays and organize something to do. A trap for people to watch out for if they suffer headache regularly — and perhaps particularly migraine — is that of analgesic over-use. Over time, many patients increase their use of over-the-counter or even prescribed medications to a point where they get a ‘rebound headache’: as the dose of the headache medication wears off the headache comes back and more medication is taken. A vicious cycle commences that may require medical intervention.

A doctor who is consulted about migraine will want to take a medical history to be sure of the diagnosis, compared with other forms of headache, and to make a full clinical examination. The approximate rule for headache action is that new or changing headache, especially of sudden onset, requires urgent attention, while persistent long-standing headache requires time, patience, and thought when planning management. Among the many other questions that might be asked, one of the most important pieces of information can be what medication has been used in the past, in what amounts, and for how long.

With detailed information from the patient about the nature and pattern of the pain, and with knowledge gleaned from experimental work from the last ten to fifteen years, migraine is now relatively well understood and can be better managed than at any time in the last 4000 years. Treatments include preventative medicines and those for use in acute attacks. The preventative medicines are drawn from a number of other areas of medical practice; migraine is not caused by high blood pressure, depression, or epilepsy, but the drugs used in treating these conditions work also in migraine and should be viewed as anti-migraine drugs. (Thus they include b blockers, serotonin blockers, antidepressants, or anticonvulsants.) For acute attacks, there are the common pain-killers such as aspirin or paracetamol, together with an anti-sickness tablet, such as domperidone, or so-called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), again with an anti-sickness medicine. There are also drugs specific for migraine, and for a rare form of headache called cluster headache, but not generally useful for other headaches, there are the ergot derivatives, and the family of triptans. The triptans were developed specifically for migraine and are certainly the most effective and best studied medicines for the condition.

There is currently considerable research into the condition. It is better understood than it has ever been, and this level of knowledge deepens with time. As understanding improves so does treatment.

Peter J. Goadsby

Bibliography

The Migraine Trust and Migraine Action Association (UK) and The American Council for Headache Education (USA) publish various information for sufferers and doctors.
Goadsby, P. J. and Silberstein, S. D. (ed.) (1997). Headache. Butterworth-Heinemann, New York.
Lance, J. W. and and Goadsby, P. J. (1998). Mechanism and management of headache, (6th edn). Butterworth-Heinemann, London.

See also headache.